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Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme
- Source :
- EBioMedicine, Vol 33, Iss, Pp 49-56 (2018), EBioMedicine
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Purpose We investigated serum cytokine and T-cell responses directed against tumour-associated antigens (TAAs) in association with survival of patients with glioblastoma multiforme (GBM). Patients and Methods Peripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A). Patients were followed-up for at least 1000 days post-surgery. Survivin protein and gene expression in resected GBM tumour tissue were confirmed by immunohistochemistry and real-time polymerase chain reaction, respectively. Antigen-specific T-cell responses were gauged by ICS (intracellular cytokine production). Associations between patient survival and immunological reactivity patterns were analysed using univariate and multivariate statistics. Results Approximately 2% of patients with GBM and 18% of patients with non-GBM glioma, were alive beyond 1000 days of surgery. Univariate analysis indicated that the combination of three cytokines (IL-4/IL-5/IL-6, p = .0022; IFN-γ/TNF-α/IL-17A, p = .0083) but not a ‘partial’ combination of these cytokines, the IFN-γ immune response to EBV-EBNA-1 (p<br />Highlights • Cytokine combinations of IL-4/5/6 or IFN-γ/TNF-α/IL-17A may predict survival in patients with GBM. • IL-2/15/21-amplified survivin peptide-specific T-cell responses may independently predict survival among patients with GBM. • Large-scale clinical studies to validate these readouts as biomarkers of survival in GBM are warranted.
- Subjects :
- Adult
Male
0301 basic medicine
Adolescent
Survivin
medicine.medical_treatment
Lymphocyte
lcsh:Medicine
Glioblastoma multiforme
General Biochemistry, Genetics and Molecular Biology
Inhibitor of Apoptosis Proteins
Young Adult
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
Glioma
medicine
Humans
Immune response
Aged
Aged, 80 and over
lcsh:R5-920
Brain Neoplasms
business.industry
lcsh:R
General Medicine
Immunotherapy
Middle Aged
medicine.disease
Survival Analysis
030104 developmental biology
medicine.anatomical_structure
Cytokine
Survival benefit
Cytokine networks
030220 oncology & carcinogenesis
Cancer research
Cytokines
Immunohistochemistry
Female
Neoplasm Grading
Glioblastoma
lcsh:Medicine (General)
business
Research Paper
Subjects
Details
- ISSN :
- 23523964
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....bb89a3a51fef3c56fc9f470d2d189e3c